| Objective:(1)Retrospective analysis of the prevalence and risk factors of low level viremia in patients with chronic hepatitis B after long-term antiviral treatment with NAs.(2)To evaluate the efficacy and safety of switching strategies in patients with low level viremia.Methods:(1)A total of 532 CHB patients who were treated with nucleos(t)ide analogues for more than one year in the first affiliated Hospital of Hainan Medical College from August 2021 to December 2021 were screened for highly sensitive HBVDNA,serum HBVDNA less than 10IU/ml was defined as complete virological response,serum HBVDNA > 10IU/ml but lower than 2000IU/m L defined as low level viremia,serum HBVDNA > 2000IU/ml was defined as poor response.Among them,326 patients with complete virological response,184 patients were in low level viremia.The general data(age,sex,History of drinking,family history),liver biochemical index,virological index,type of antiviral drugs and drug compliance during treatment in the two groups were retrospectively analyzed to explore the risk factors of low level viremia caused by long-term nucleos(t)ide analogues treatment.(2)A total of 184 patients with low level viremia were randomly assigned to the control group who maintained the origined NAs and the patients who changed the treatment strategy as the experimental group,and the related indexes(HBVDNA undetectable rate,HBs Ag decline rate,serum HBe Ag negative conversion rate,ALT normalization rate,liver hardness change,etc.)of the two groups were observed at 12 weeks,24 weeks and 48 weeks to evaluate the efficacy and safety of the control group and the experimental group.Results:(1)Among the 532 CHB patients who were screened for highly sensitive HBV DNA,326 patients obtained complete viral response,184 patients were in low level viremia,22 patients had poor response,and the incidence of low level viremia was 34.59%.(2)The incidence of low level viremia after antiviral therapy with non-first-line nucleos(t)ide analogues was significantly higher than that with first-line nucleos(t)ide analogues(P < 0.05),while the incidence of low level viremia among tenofovir alafenadide fumarate subgroups treated with first-line nucleos(t)ide analogues antiviral therapy was the lowest.(3)By comparing the general data and clinical indexes of patients in complete viral response group and low level viremia group before starting antiviral therapy,it was found that there were significant differences in age,family history of liver cirrhosis,baseline viral load,HBs Ag level,HBe Ag positive,type of antiviral drugs,medication time and drug compliance(P<0.05).(4)Univariate analysis showed that high baseline viral load,high HBs Ag quantitative level,positive serum HBe Ag,poor drug compliance during nonfirst-line nucleos(t)ide analogues use and antiviral therapy were independent risk factors for low level viremia(P<0.05).(5)The complete viral response rate of low level viremia patients was higher than that of the original treatment regimen after 48 weeks of switching to antiviral therapy.(59.3% VS 40.8%,P=0.014).(6)Among the patients who converted to antiviral therapy strategy,there was significant difference in the proportion of patients who were converted to tenofovir alafenadide fumarate,tenofovir disoproxil fumarate and entecavir for48 weeks(P < 0.05).The complete virological response rate and ALT normalization rate were higher after conversion to tenofovir alafenadide fumarate.(7)After 48 weeks,the decrease of HBs Ag in the antiviral treatment group was significantly higher than that in the original treatment group(P < 0.05).(8)At the end point of observation,there was no significant difference in serum HBe Ag negative conversion rate and liver FIB-4 score between the two treatment strategies(P>0.05).(9)During the whole observation period,the safety of the two treatment strategies was good,and no serious adverse reactions occurred.Conclusion:(1)Even if there is a risk of low level viremia after long-term nucleos(t)ide analogues treatment,high baseline HBVDNA load before initial treatment,high HBs Ag quantification,positive serum HBe Ag,non-first-line nucleos(t)ide analogues and poor drug compliance during treatment are independent risk factors for low level viremia.CHB patients with the above risk factors need regular screening of highly sensitive q PCR to understand the level of serum HBVDNA after treatment.(2)The first-line nucleos(t)ide analogues drug therapy recommended in the guidelines for initial treatment has a relatively low incidence of low level viremia.Compared with entecavir and tenofovir disoproxil fumarate,tenofovir alafenadide fumarate can get a higher virological response in a shorter treatment time,and the incidence of low level viremia is relatively low.(3)The conversion strategy for low level viremia can obtain better complete virological response rate,ALT normalization rate,HBs Ag reduction and better safety than maintaining the initial treatment plan.Compared with entecavir and tenofovir disoproxil fumarate,tenofovir alafenadide fumarate has higher ALT normalization rate and virological response rate. |
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